Changes in the preload or rest length of vascular smooth muscle (VSM) are known to alter the sensitivity of VSM to vasoactive agents. Increases in preload cause decreases in the EC50 of rat and rabbit aorta as well as canine tibialis arterial muscle. The mechanism responsible for this stretch-induced change in sensitivity is not known. One possibility is that prostaglandins mediate the response. According to this hypothesis, stretch causes an increase in prostaglandin production and, consequently, one or more of these prostaglandins alters the sensitivity of VSM to contractile agents. This hypothesis will be explored 1) by determining what effects are exerted on rat aortic smooth muscle sensitivity by alterations in endogenous prostaglandin production, 2) by identifying specific prostaglandins or metabolites which could serve as mediators of the stretch effect in rat aorta, 3) by ascertaining whether exogenous prostaglandins mimic the effect of stretch on aortic smooth muscle sensitivity, 4) by determining whether prostaglandins play the same role in other VSMs which also exhibit the stretch response (e.g. rabbit aorta and canine tibialis artery). The effect of stretch on sensitivity appears to be a fundamental property of VSM and a determination of its underlying mechanism would increase our knowledge of VSM physiology in general. In particular, the interaction between wall stress and prostaglandin production may be important not only for the metabolism of aortic smooth muscle in certain pathological states (e.g. hypertension and atherosclerosis), but also in the normal control of blood flow.